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Biomedical subjects

I Rasanen

Publications and source records attributed to I Rasanen.

8 recordsLinked to original sources
PubMed2003

Precise gas chromatography with retention time locking in comprehensive toxicological screening for drugs in blood.

The long-term precision of three retention parameters, the absolute retention time (RT), the relative retention time related to dibenzepin (RRT), and the internal retention index based on the alkylfluoroaniline series (RI), were studied with 14 basic drugs on HP-5 and DB-17 columns with and without the use of the retention time locking option (RTL). Using the constant flow mode in all experiments, the RTL method was found to produce superior precision with all three retention parameters compared to the non-RTL method on each column. The results showed that RTL offers a significant advantage within a single instrument method, not only between methods, with CV<0.1% by RRT. Consequently, a dual-column gas chromatographic procedure with nitrogen-phosphorus detection was described for comprehensive screening for basic drugs in 1-ml whole blood samples. The method consisted of one-step liquid-liquid extraction with butyl acetate, identification using RRT in the RTL mode, and quantification based on single point calibration. The method allowed reliable screening and quantification of 124 basic drugs at therapeutic and toxic concentration levels in autopsy blood.

Chromatography, Gas↗
PubMed2000

Benzodiazepine findings in blood and urine by gas chromatography and immunoassay.

Gas chromatography (GC) and immunoassay techniques applied to blood and urine specimens were compared for the screening of benzodiazepines in postmortem forensic toxicology. Five hundred and six such successive postmortem cases in which both urine and peripheral blood was sent for toxicological analysis by the medical examiners were selected. The urine specimens were tested by the Emit((R)) d.a.u. Benzodiazepine Assay, and in parallel, the blood and urine specimens were screened for benzodiazepine drugs and their metabolites by an established automated dual-column GC method. The lowest number of positives (153) was obtained when immunoassay was performed without enzyme hydrolysis. When urine samples were hydrolysed before immunoassay, the number of positives increased to 175. The highest number of positives (200) was obtained in urine by GC, and the screening of blood by GC yielded 185 quantitative results. Despite the urine GC screening produced the most positives, the quantitative screening of the blood by GC appears to be the most efficient approach in postmortem forensic toxicology, considering the fact that although urine findings confirm the presence of the drug, quantitative results in urine are irrelevant to acute toxicity.

Anti-Anxiety Agents↗
PubMed1999

Identification of the major tamoxifen-DNA adducts in rat liver by mass spectroscopy.

We present here the first mass spectroscopic (MS) identification of the main tamoxifen-induced DNA adducts in rat liver. The two main adducts were isolated by high-performance liquid chromatography (HPLC) and identified by MS, MS-MS and ultraviolet spectroscopy. Adduct 1 was the N-desmethyltamoxifen-deoxyguanosine adduct in which the alpha-position of the metabolite N-desmethyltamoxifen is linked covalently to the amino group of deoxyguanosine. Adduct 2 was confirmed to be the trans isomer of alpha-(N2-deoxyguanosinyl)tamoxifen, as previously suggested by co-chromatography.

Animals↗
PubMed1999

Butadiene diolepoxide- and diepoxybutane-derived DNA adducts at N7-guanine: a high occurrence of diolepoxide-derived adducts in mouse lung after 1,3-butadiene exposure.

Butadiene (BD) is a high production volume chemical and is known to be tumorigenic in rodents. BD is metabolized to butadiene monoepoxide (BMO), diepoxybutane (DEB) and butadiene diolepoxide (BDE). These epoxides are genotoxic and alkylate DNA both in vitro and in vivo, mainly at the N7 position of guanine. In this study, a 32P-post-labeling/thin-layer chromatography (TLC)/high-pressure liquid chromatography (HPLC) assay for BDE and DEB adducts at the N7 of guanine was developed and was used in determining the enantiomeric composition of the adducts and the organ dose of BD exposure in lung. Exposure of 2'-deoxyguanosine (dGuo), 2'-deoxyguanosine-5'-phosphate (5'-dGMP) and 2'-deoxyguanosine-3'-phosphate (3'-dGMP) to racemic BDE followed by neutral thermal hydrolysis gave two products (products 1 and 2) that were identified by MS and UV and NMR spectroscopy as a diastereomeric pair of N7-(2,3,4-trihydroxybutan-1-yl)-guanines. Exposure of dGuo nucleotides to RR/SS DEB (also referred to as dl DEB) followed by thermal depurination resulted in a single product coeluting with the BDE product 1. If the reaction mixture of BDE and 5'-dGMP was analyzed by HPLC before hydrolysis of the glycosidic bond, four major nucleotide alkylation products (A, B, C and D) with identical UV sepectra were detected. The products were isolated and hydrolyzed, after which A and C coeluted with product 1 and B and D coeluted with the product 2. The major adduct of DEB-exposed 5'-dGMP was N7-(2-hydroxy-3,4-epoxy-1-yl)-dGMP (product E). A 32P-post-labeling assay was used to detect BDE- and DEB-derived N7-dGMP adducts in DNA. Levels of adducts increased with a dose of BDE and DEB and exhibited a half life of 30 +/- 3 (r = 0.98) and 31 +/- 4 h (r = 0.95), respectively. Incubation of DEB-modified DNA at 37 degrees C at neutral pH for up to 142 h did not lead to an increase of N7-(2,3,4-trihydroxybutan-1-yl)-dGMP in the DNA. These observations led to the conclusion that the N7-(2,3, 4-trihydroxybutan-1-yl)-dGMP adducts in DNA can be used as a marker of BDE exposure and that N7-(2-hydroxy-3,4-epoxy-1-yl)-dGMP adducts are related to DEB exposure. Dose-related levels of BDE- and DEB-derived adducts were detected in lungs of mice inhaling butadiene. Most of the N7-dGMP adducts (73%; product D) were derived from the 2R-diol-3S-epoxide of 1,3-butadiene. The data presented in this paper indicate that in vivo, 98% of N7-dGMP alkylation after BD exposure is derived from BDE, and approximately 2% of the adducts were derived from DEB and BMO.

Animals↗
PubMed1996

Comparison of four homologous retention index standard series for qualitative gas chromatography of nitrogenous acidic and neutral drugs.

Four homologous retention index standard series, the alkylmethylhydantoins, alkylhydantoins, alkylmaleimides and alkylbis(trifluoromethyl)phosphine sulphides, were evaluated for the screening of blood samples for acidic and neutral drugs on Ultra 2 and HP-1701 capillary columns over a six-month period. An index series consisting of actual drug substances was used as a standard of comparison. All the series produced high precision, and the precision differences between the series were rather small. Considering the limitations of the other series, the alkylmethylhydantoins and alkylhydantoins turned out to be the most feasible internal retention index standard series in the present dual column setting.

Blood Chemical Analysis↗
PubMedDate not supplied

Automated quantitative screening for acidic and neutral drugs in whole blood by dual-column capillary gas chromatography.

A method consisting of single-step extraction, dual-channel capillary gas chromatography, nitrogen-selective detection, and automated data processing is evaluated for the quantitative screening of acidic and neutral drugs in postmortem blood. The drugs are identified by their cubic spline retention indices using multidetector retention index standards. The data processing is performed with Micman software, which offers several advantages in the maintenance of identification reliability. The precision of the retention indices during a three-month period with a routine loading of 14 samples per day is presented for eight different drugs at therapeutic and toxic concentrations: The CV ranges from 0.11% to 1.12% for NB-54 and from 0.05% to 0.21% for NB-1701. The within-day CV is less than 0.05% in each case. The status of these results and the means of achieving further precision are discussed. The long-term precision of quantification, normally under 10%, is considered adequate for most forensic toxicological purposes.

Chromatography, Gas↗
PubMedDate not supplied

Quantitative screening for benzodiazepines in blood by dual-column gas chromatography and comparison of the results with urine immunoassay.

A dual-column retention index method is described for quantitative gas chromatographic (GC) screening of 26 benzodiazepine drugs and metabolites in the blood using DB-5 and DB-17 capillary columns and electron capture detection. The method involves a one-step, small-scale liquid-liquid extraction with ethyl acetate and derivatization with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide with 1% tert-butyldimethylsilyl chloride. The results from the GC screening of 514 postmortem blood samples were compared to those obtained from urine immunoassay (Syva ETSplus with a 200-ng/mL cutoff). Both methods gave a negative result in 284 cases and a positive result in 149 cases. In 48 cases, urine was negative by immunoassay but blood was positive by GC. The opposite situation (blood negative, urine positive) was detected only in four cases. In 29 cases, an invalid result was obtained by urine by immunoassay: 26 blood samples of those cases were negative and three samples positive by GC. In postmortem forensic toxicology, the present GC method seems to be a good alternative to the common combination of urinary immunoassay followed by quantitative analysis of blood by chromatography.

Acetamides↗